(Applicant's Abstract) The overall purpose of this SCOR proposal is to investigate the role of the myofibroblast in idiopathic pulmonary fibrosis (IPF). We are particularly interested in defining the source and regulation of TGF-beta production, especially the contribution of the ingestion of apoptotic cells and cell debris, the relationship of paracrine factors and mechanical factors on myofibroblast gene regulation, the role of survival factors for myofibroblasts such as IGF- I and myofibroblast apoptosis, interactions of myofibroblasts with alveolar epithelial cells, and finally regulation by interferon gamma (INF). In the clinical portion of this SCOR proposal, Dr. Schwarz will evaluate INF in the treatment of idiopathic pulmonary fibrosis. A major aspect of this proposal will be to use DNA microarrays to define gene expression of specific cell types as well as alterations in fibrotic lung and microdissected fibroblastic foci in IPF and Masson bodies in BOOP. In project 1, Dr. Henson will study the regulation of TGF-beta production by the ingestion of apoptotic cells. This is a new biologic process for the production of TGF-beta. In project 2, Dr. Worthen will study the regulation of the myofibroblast phenotype especially the interaction between paracrine factors such as TGF-beta and mechanical stress. In project 3, Dr. Riches will determine the role of IGF-1 as a survival factor which prevents the apoptosis of myofibroblasts. In project 4, Dr. Mason will study the interactions between myofibroblasts and alveolar type II cells. A significant portion of this project is to define the interactions between KGF, TGF-beta, and INF on the alveolar epithelium. In project 5, Dr. Schwarz will determine the clinical efficacy of INF as therapy for idiopathic pulmonary fibrosis, myofibroblast proliferation and apoptosis in IPF, and gene expression in fibroblastic foci in IPF and Masson bodies of BOOP.